The goal of this Program of Excellence for Basic Research on AIDS is to understand at the molecular level the activation of Human Immunodeficiency Virus (HIV) from a state of latency to pathogenic expression. This understanding will be accomplished by an interdisciplinary approach involving studies in genetics, molecular and cell biology, biochemistry, and structural studies. The program is composed of seven individual sections: the Viral Genetics project will define the regulatory elements within the HIV promoter; the Signal Transduction project will define the signal transduction pathways in T cells responsible for HIV activation; the Cellular Transactivators project (Franza) will study the cellular transactivators involved in activation of the HIV promoter; the Viral Transactivators project will study the structure and function of the viral transactivator tat and its role in HIV activation; the Transcription project (Hernandez) will study the elements and cellular factors responsible for TAR function, which allow tat transactivation of HIV; the Transgenic Mice project will develop animal models to study the cis-acting HIV/LTR promoter elements and the effects of tat transactivation in vivo; the Structural Molecular Biology project will determine the X-ray crystallographic structures of both viral (tat) and (fos) transactivators of HIV gene expression. The structural studies form a cornerstone of this program as it is the interchange between functional studies and X-ray crystallographic studies that will guarantee the long-range success of this program and is most likely to lead to the rational design of drugs that will interfere with HIV activation.